Downregulation and upregulation

Downregulation is the process by which a cell decreases the number of receptors to a given hormone or neurotransmitter to reduce its sensitivity to this molecule. An increase of receptors is called upregulation.

To illustrate this process we shall look at the insulin receptor sites on the target cells of a Type II diabetic. Due to the elevated levels of blood glucose from excessive feeding in an overweight individual the beta cells in the pancreas must release more insulin than normally emitted to match the demand and return the blood to homeostatic levels. The near constant increase in blood insulin levels results from an effort to match the increase in blood glucose which will cause receptor sites on the person’s cell to downregulate and decrease the number of receptors for insulin, increasing the subject’s resistance by decreasing sensitivity to this hormone. There is also a hepatic decrease in sensitivity to insulin. This can be seen in the continuing gluconeogenesis in the liver even when blood glucose levels are elevated. This in turn leads to a case of adult onset diabetes in that subject.

There are ways to counteract this process; using the previous example a Type II diabetic may increase their sensitivity to insulin through proper diet and regular exercise producing weight loss, some may even return to their pre-diabetic state following this regimen.

Reference

Wilmore, J., Costill, D. (2004). Physiology of Sport and Exercise, 3rd Ed (p. 164). Champaign, IL: Human Kinetics